SummaryThe importance of calcium as a second messenger probably cannot be emphasized enough. Ca2+ signaling via Ca2+ sensors such as calmodulin regulates various vital functions in cells in response to stimuli. Calmodulin is a small, evolutionarily conserved Ca2+-binding protein of the EF-hand superfamily that participates in many different cellular pathways through the regulation of a diverse group of targets. Its function has been shown to depend greatly on how it is distributed in the cell and the pools likely allow CaM to be activated at the right time and place. Gene organization and evolutionary history The three genes encoding human calmodulin, CALM 1-3, are not -allelic and therefore located on different chromosomes, respectively 14q24-q31, 2p21.1-p21.3 and 19q13.2-q13 .3 [1]. These CaM genes have identical intron-exon boundaries, consist of six exons and encode an identical monomeric CaM protein of 148 amino acids (fig. 1), but transcribed into at least 7 different major mRNAs differentiating with respect to polyadenylation alternative. among the transcripts of each gene [2]. In addition to the three known CALM genes, the human CaM/CaM-like gene family contains numerous pseudogenes and calmodulin-like proteins [1]. CaM is a highly evolutionarily conserved protein found in all eukaryotic cells (Fig. 2). Since CaM belongs to the EF-hand protein superfamily (Fig. 1), its main structure originated before branching into plants, fungi, invertebrates, and vertebrates. It is likely that this occurred when two gene duplications followed by a fusion led to four EF hands joining together into a single structure. Other modifications that explain the invariant CaM in vertebrates [2] and later the three true mom CaM genes...... middle of article ......n long-term potentiation[12 ]Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique NaV1.5 sodium channel[15]Modulation of calmodulin plasticity in molecular recognition based on structure , A. (2013): The many faces of calmodulin in cell proliferation, programmed cell death, autophagy and cancer[19] Alterations of Ca2+/calmodulin/CaMKII/CaV1. 2 signaling in experimental models of Alzheimer's disease and vascular dementia